Eventually, Wilson's activities as a trade unionist attracted the attention of the mine operators. In the spring of 1882, Wilson was a correspondent for the Elmira Telegram, a weekly paper, writing of the births, deaths, marriages, and other Arnot news. A series of articles appeared in the paper with an Arnot byline. Incorrectly suspecting Wilson as the author, the mine operator decided to fire him, using slack business as an excuse. Blacklisted for a time in Tioga County, Wilson went to Iowa to seek work and a pattern of irregular employment was established, although he continued his union activism.

From 1882 to 1900, Wilson traveled to many parts of the country looking for work and promoting unions. He dug ditches, worked as a lumber jack, wood chopper, bark peeler and log driver. He drifted West, and became a fireman on the Illinois Central Railroad for a time. At one point, he worked in a printing office in Blossburg setting type on a newspaper, where he learned punctuation, capitalization, and grammar. These experiences broadened his perspective on labor issues. Wilson wrote, "For some reason or another, I was unable to hold a job for more than a few weeks at a time. No fault was found with my work but my services were not wanted."

On June 7, 1883, Wilson married Agnes Williamson, an Arnot resident and fellow Good Templar member, who was also born in Scotland. William and Agnes had eleven children. The Good Templars was a temperance organization. He wrote, "I would work at whatever I could find to do at home to keep my bills paid up and be ready to go whenever the call for help came... We lived in the most humble way and although my wife was a wonderful manager, we were often badly pinched for the means of living."

During this period of labor activism, Wilson traveled extensively in Pennsylvania, New York, and Maryland assisting striking miners, establishing joint conferences between operators and miners (a precursor to the collective bargaining system), and organizing union locals. He was elected to the executive committee of the central Pennsylvania district of the Amalgamated Association of Miners and Mine Laborers, a part of the American Federation of Miners, and also to the position of District Master Workman of the Knights of Labor, another union with which he had been involved since his teenage years. In 1888, Wilson attempted to combine the two organizations into the National Progressive Union, but the Knights of Labor remained a separate organization. Finally, in 1890, he convinced the executive board of the Knights to meet with the Progressive Union to fully unite. Wilson became chair of the constitutional and by-law committee and on January 25, 1890, the United Mine Workers of America was formed. He was elected a member of the UMWA's National Executive Board in 1891 and again in 1894. [Ed. note: The UMWA's constitution, the committee of which Wilson was chair, specifically prohibited discrimination based on race, religion, or national origin, unusual for this time when Jim Crow laws were strictly enforced.]

As one of its first campaigns, the UMWA tried to create a movement for an eight-hour workday. However, the workers were not ready to undertake the battle and the issue was temporarily dropped. In 1896, Wilson was able to create a contract between miners and mine operators in central Pennsylvania that included a clause for an eight-hour day.

As he traveled, he stayed with miners who were willing to risk losing their jobs by hosting him, and many did. He was frequently jailed for his work, as were many progressive agitators of the time. Wilson advocated peaceful settlement of strikes, often interfering with militant workers' plans to use force to settle a labor dispute.

Once he was tricked aboard a train by agents of the mine owners and taken to Cumberland, Md., thrown into jail on charges of conspiracy, but in three days they were forced to release him. Upon defying a court injunction Wilson said, "An injunction that restrains me from furnishing food to hungry men, women and children, when I have in my possession the means to aid them, will be violated by me until the necessity for providing food has been removed or the corporeal power of the court overwhelms me. I will treat it as I would an order of the court to stop breathing."

After the coal strike of 1894, William once again found himself blacklisted and could not secure work in the mines. He secured a farm in 1896. He worked the farm in the summer and found various jobs throughout the area in the winter. In 1899 he was re-elected President of District No. 2, but resigned in May 1900 when John Mitchell, the legendary president of the UMWA appointed him to the position of Secretary-Treasurer of the United Mine Workers of America.

Wilson was elected International Secretary-Treasurer of the United Mine Workers of America in uncontested races for the next eight years and worked closely with Mitchell, the union's fifth president.